title: Bevacizumab (BVZ)-associated toxicities in children with recurrent central nervous system tumors treated with BVZ and irinotecan (CPT-11): a Pediatric Brain Tumor Consortium Study (PBTC-022).
abstract: BACKGROUND
  The incidence and spectrum of acute toxicities related to the use of bevacizumab (BVZ)-containing regimens in children are largely unknown. This report describes the adverse events in a recently completed large phase 2 trial of BVZ plus irinotecan (CPT-11) in children with recurrent central nervous system tumors.
  
  
  METHODS
  Pediatric Brain Tumor Consortium trial-022 evaluated the efficacy and toxicity of BVZ (10 mg/kg administered intravenously) as a single agent for 2 doses given 2 weeks apart and then combined with CPT-11 every 2 weeks (1 course = 4 weeks) in children with recurrent central nervous system tumors. Children were treated until they experienced progressive disease, unacceptable toxicity or completed up to a maximum of 2 years of therapy. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Patients who received at least 1 dose of BVZ were included for toxicity assessment.
  
  
  RESULTS
  Between October 2006 and June 2010, 92 patients evaluable for toxicity were enrolled and received 687 treatment courses. The most common toxicities attributable to BVZ included grade I-III hypertension (38% of patients), grade I-III fatigue (30%), grade I-II epistaxis (24%), and grade I-IV proteinuria (22%). Twenty-two patients (24%) stopped therapy due to toxicity.
  
  
  CONCLUSIONS
  The combination of BVZ and CPT-11 was fairly well-tolerated, and most severe BVZ-related toxicities were rare, self-limiting, and manageable.
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
authors.forename: Jason
authors.initials: J
authors.lastname: Fangusaro
authors.forename: Sridharan
authors.initials: S
authors.lastname: Gururangan
authors.forename: Tina Young
authors.initials: TY
authors.lastname: Poussaint
authors.forename: Roger E
authors.initials: RE
authors.lastname: McLendon
authors.forename: Arzu
authors.initials: A
authors.lastname: Onar-Thomas
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Warren
authors.forename: Shengjie
authors.initials: S
authors.lastname: Wu
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Packer
authors.forename: Anu
authors.initials: A
authors.lastname: Banerjee
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gilbertson
authors.forename: Regina
authors.initials: R
authors.lastname: Jakacki
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
authors.forename: Stewart
authors.initials: S
authors.lastname: Goldman
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: James M
authors.initials: JM
authors.lastname: Boyett
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
authors.forename: Maryam
authors.initials: M
authors.lastname: Fouladi
mesh_terms: D000293:Adolescent; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007223:Infant; D007275:Injections, Intravenous; D000077146:Irinotecan; D009364:Neoplasm Recurrence, Local; D011507:Proteinuria / Q000139:chemically induced; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin
keywords: bevacizumab; central nervous system tumors; clinical trials; pediatric; toxicity